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[Effects of epidermal growth factor (EGF) on prostaglandin E2 synthesis by cultured human endometrial cells].

Prostaglandins are considered to participate in the nidation of the embryo. However, so far little is known about the regulation of prostaglandin synthesis in endometrial tissue. In this study, we examined the effect of epidermal growth factor (EGF) on the release of PGE2 with primary cell culture of human endometrium. EGF stimulated PGE2 release dose-dependently in the range between 0.1 ng/ml and 100 ng/ml. PGE2 release was augmented significantly as early as 30 minutes after the addition of EGF, reaching a plateau at 3 hours. The stimulatory effect of EGF was eliminated by the concomitant addition of lipocortin, an inhibitor of phospholipase A2. However, the effect of EGF was not influenced by cycloheximide. Estradiol alone had a weak effect on PGE2 release. However, the stimulatory effect of EGF was more pronounced in cells pretreated with estradiol. In conclusion, this report offers evidence that EGF stimulates the release of PGE2 from human endometrial cells, thus implying the involvement of EGF in implantation.

Adult↗

[Preliminary study on 4 indices of basal body temperature in the evaluation of luteal phase insufficiency after clomiphene treatment].

The luteal phase insufficiency after Clomiphene treatment in 90 patients with polycystic ovary syndrome (PCOS) and other menstrual disorders was evaluated by four indices of BBT. The four indices of BBT are (1) BBT curve classification; (2) High phase score (HPS); (3) Planimetric nidation index (PNI); (4) Length of follicular phase. 90 patients (248 cycles) were divided into two groups: non-pregnant group (214 cycles) and pregnant group (34 cycles). The result indicated that 70% cycles of non-pregnant group, the types of BBT are type III-VI, HPS is less than 9; the mean value of PNI is 45.7; the follicular phase lists beyond 17 days, with a mean of 18.6 days. More than two-thirds of the study cycles are abnormal at least in two indices. In all cycles of the pregnant group, BBT curve are of type I, II, HPS greater than 9, PNI greater than 57. The results suggest that measurement of the four indices of BBT is a simple method which could be widely used for the evaluation of luteal phase insufficiency.

Body Temperature↗

Rabbit endosalpinx suppresses ectopic implantation.

This study was undertaken to elucidate the mechanism underlying the absence of oviductal ectopic pregnancies in infraprimates. Endosalpingeal circumferential grafts were substituted for endometrium in a group of rabbits. The endosalpingeal grafts interfered with implantation as evidenced by four observations: (1) The nidation indices were lowered, (2) no implantations occurred on the grafted endosalpinx, (3) unattached blastocysts were found in animals grafted with endosalpinx, and (4) the implantation sites were significantly smaller in uterine horns containing endosalpingeal grafts. These findings suggest the presence of a factor in rabbit endosalpinx that actively suppresses ectopic implantation in the oviduct.

Animals↗

Fibrin glue vs. nylon in the anastomosis of rabbit fallopian tubes.

Fibrin glue was used in end-to-end tubal anastomosis on eight sexually mature female New Zealand white rabbits. The right fallopian tubes were anastomosed with 10/0 nylon and the left with fibrin glue (Tissucol). The animals were mated with males of proven fertility six weeks after surgery and killed two weeks later. The gestational sacs and corpora lutea on the right and left sides were counted separately and the nidation index calculated for each. The presence of adhesions was also evaluated. All the tubes were finally examined under a scanning electron microscope. The fibrin glue was satisfactory in terms of patency, pregnancy and morphology of the epithelium.

Animals↗

Encouraging rates of fertility after ectopic pregnancy.

A follow-up study (4 to 8 years) on fertility of 110 patients seeking pregnancy after ectopic pregnancy (EP) showed normal delivery in 65%, recurrent EP in 20%, and infertility in 15%. Delivery rates were better in patients who were under age 30 years, used an IUD at the time of operation for EP, and underwent conservative operative treatment for acute EP. The subsequent intrauterine pregnancy rates of EP patients who had used an IUD at the time of ectopic nidation were the same (92%) as after removal of IUD in the healthy population. It appears that IUD plays a predisposing role in EP only when in use. The study also shows that modern diagnostic and therapeutic procedures are beneficial for improving subsequent fertility rates after EP. These fertility rates are highly encouraging with respect to the massive increase of EP in the Finnish population.

Adult↗

[Forensic medicine aspects of surrogate mothers and artificial insemination].

Artificial insemination solves the problem of childlessness in a way never before thought possible. There is now often a lack of guiding principles in law, and new ethical questions have arisen. It would appear that homologous insemination is the simplest. This is recognized by the church; by doctors, even for unmarried couples. Heterological insemination, on the other hand, is only rarely acceptable to married couples, and then subject to the limits of generation, the avoidance of half-brothers and sisters, and gamete mistakes, as well as any commercialization. The medical standpoint and other legal developments must be reconciled with these factors; particularly the possibility of cancelling the anonymity of the sperm donor and the right to appeal of the social father. As a general principle, the ruling premise should be to place the burden of risk on the parents. With in-vitro fertilization, the existence of surplus embryos is particularly problematic. It is becoming more and more common to regard life as commencing in the zygote and not in the nidation. Can the scientific experiments permitted under the new professional regulations-even with more complicated requirements-be reconciled with this? Consensus can be reached in rejecting surrogate motherhood, since the danger of commercialization is too great, and propagation possibilities are being opened up which, to our present understanding, are irresponsible.

Expert Testimony↗

Future growth and development of hysteroscopy.

In less than two decades, hysteroscopy has evolved into a practical technique for the evaluation of the uterine cavity, with well-established indications such as evaluation of abnormal uterine bleeding and abnormal hysterograms as well as the treatment of intrauterine adhesions or the septate uterus, the removal of misplaced or embedded intrauterine devices, and the removal of submucous leiomyomas. As the use of hysteroscopy increases and more practitioners utilize it, new instrumentation and techniques are beginning to evolve, simplifying and facilitating not only a diagnostic examination, but also the more difficult and complex surgical interventions. Flexible endoscopes are being tested for possible use in the uterine cavity, and operative hysteroscopes with practical inflow and outflow accessory channels have been introduced. The accessory operative instrumentation has also been expanded and refined, and portable units for office examinations have been developed. The trend in the development of instrumentation is toward simplicity, effectiveness, and refinement in lenses with wider fields of view and accessory channels without compromising the total outer diameter of the endoscopes. As clinical applications expand as a result of increased use and proficiency in hysteroscopy, new applications undoubtedly will follow, such as closer study of the endometrium with and without additional magnification. This latter may permit a better understanding of the receptivity of the endometrium to the embryo, which may help in predicting successful nidations. Portable laser units with the capability to use the CO2 fiber undoubtedly will increase laser use through hysteroscopy, and in the near future, photodynamic therapy may become the best approach to the selective treatment of intrauterine lesions. The uterotubal junction will remain an attractive area for endoscopists to approach the fallopian tubes transcervically and eventually to accomplish tubal closure safely and effectively with the possibility of future reversibility. The hysteroscope will play an important role in new reproductive technologies, particularly those related to the gamete intrafallopian transfer via the uterine side and perhaps also for direct embryo transfers under visual control. The future of hysteroscopy thus is promising. The present diagnostic and therapeutic applications will not only become a standard of treatment but will expand as gynecologists will gain proficiency and confidence in this endoscopic method.

Endoscopes↗

Intrauterine steroid contraceptives.

Progestagen releasing IUDs were specially developed to diminish the problems of bleeding and pain with inert and copper containing IUDs. The intrauterine release of the progestagen causes endometrial atrophy, resulting in impairment of nidation, and interferes with transport of the ovum and the spermatozoa. Two available types, Progestasert, Biograviplan (Alza Corporation, California; Grünenthal) and Levonorgestrel Nova-T (Leiras Pharmaceuticals, Finland), have been sufficiently tested in multinational trials. Compared with Progestasert, LNG Nova-T showed lower pregnancy rates (Pearl Index 0.30), less risk for ectopic pregnancy and a longer effective lifetime (7 years). With both IUDs the amount and duration of menstrual blood loss is decreased. Amenorrhea is a frequent occurring side effect of LNG Nova-T, caused by endometrial atrophy. Intermenstrual blood loss and spotting incidences are not uniformly reduced and are still a frequent reason for removal. Preinsertion counselling may improve the acceptance of these non-health-threatening side effects. With both IUDs a decrease of menstrual cramps during periods is percepted and a low incidence of PID is found. Basically, the progestagen releasing IUD can be recommended to all women who wish an IUD for contraception and to women with contraindications for oral contraceptives, especially to those with menorrhagia, anaemia or risk for anaemia.

Contraceptive Agents, Female↗

Glycoconjugate distribution in normal human endometrium. A lectin histochemical study.

A battery of nine lectins was applied to routinely processed endometrial biopsies to evaluate changes in glycoconjugate expression during the menstrual cycle and early gestation. Specific staining patterns emerged for glands, surface epithelium, predecidual and decidual cells, stromal granulocytes, and endothelium. Three lectins--wheat germ agglutinin (WGA), Ricinus communis-I (RCA-I), and Concanavalin ensiformis (Con-A)--showed consistent binding to epithelial and stromal cells in the menstrual cycle. WGA and RCA were bound to gland secretions whereas Con-A labeled epithelial cytoplasm. These three lectins stained occasional stromal cells early in the cycle, but WGA and RCA marked granulocytes whereas Con-A labeled predecidua in the late secretory phase. Succinylated WGA had a distribution similar to WGA but lacked its consistency and intensity. In the menstrual cycle peanut agglutinin reacted with ciliated cells. In addition, this lectin along with soybean agglutinin and Dolichos biflorus labeled gland secretions in pregnancy. The remaining lectins, Phaseolus vulgaris leucoagglutin and Ulex europaeus, marked some components, especially endothelium, but generally had less reactivity than the other lectins did. The results indicate that glycoconjugate production is correlated with the functional status of the endometrium. Presumably these glycoconjugates play a role in endometrial development necessary for nidation, and alterations in lectin distribution may reflect functional abnormalities not apparent by light microscopic study.

Adult↗

Cellular aspects of in vitro fertilization (ultrastructural and cytogenetic studies of human gametes and zygotes).

After the birth of Louise Brown in 1978 as a result of the successful development of in vitro fertilization (IVF) techniques by Edwards and Steptoe, the use of this procedure has become extremely widespread, both in technologically advanced societies and even in countries that do not meet the minimal sanitary standards. In good hands, IVF techniques provide results slightly lower than those allowed by nature, that is about 20% of pregnancies. In other cases, the procedure may become a nightware coupled to a swindle, and even endanger the life of the hopeful mother-to-be. Even in the better prepared centers, with the highest rates of success, IVF is still surrounded by a myriad of problems that must be solved to optimize its results and to reduce the risk of zygotic loss and of multiple pregnancies. On the other hand, IVF offers unimagined possibilities for research on fields of such interest as the reasons for the high incidence of nidation and/or developmental failures of human zygotes, the high percentage of infertile or sterile couples, pre-implantation diagnosis and gene therapy. These problems will only be solved if research in human cell aggregates (also called pre-embryos) is allowed. The potential medical, human and social benefits of such research is considerable, and could have diagnostic and therapeutical applications in a short period of time. There are many possible causes of infertility or sterility: genetic, cellular, immunological, hormonal, developmental, etc. This volume includes the results of ultrastructural and cytogenetic studies of human gametes and zygotes, and tries to shed some light on the origin of IVF failures. The use of a murine model for the study of the first zygotic division has also provided data on possible mechanisms resulting in abnormal zygotes, like hormonal unbalance or gamete aging. The morphological and genetic characteristics of the sperm in the father, and the age of the gamete, the hormonal balance, the genetic endowment of the oocyte, and the induction of superovulation in the mother seem to be important factors both when in vitro fertilization does not take place or when abnormal zygotes are produced.

Acrosome↗

Antihypertensive ergoline derivatives.

Novel ergolines were synthesized and screened in spontaneous hypertensive rats (SHR) with the aim of finding a new class of ergot related antihypertensives. Their prolactin inhibitory effect (measured as nidation inhibition in rats), acute toxicity (LD50) and interference with CNS function (Irwin test) were also evaluated as a measure of selectivity and safety. Modification of the C8 side-chain enhanced antihypertensive activity selectively, while the introduction of substituents in other positions of the ergoline skeleton generally yielded unfavourable results, either by decreasing selectivity or by increasing toxicity.

Animals↗

Estrogen receptor binding material in blood of patients after clomiphene citrate administration: determination by a radioreceptor assay.

The aim of the current study was to assess whether clomiphene citrate (CC) and/or active metabolites are present at presumed time of ovulation, nidation, or steroid-sensitive organogenesis, in serum of patients receiving CC for induction of ovulation. A radioreceptor assay, based on competitive replacement of 3H-estradiol on the rat uterus estrogen receptor, by ligands present in serum of patients after CC administration, was developed. Ligands reached maximal concentration 4 to 5 hours after a single dose of CC was administered, and declined with a half-life of 4.5 to 10 hours. In patients receiving CC on day 5 to day 9 in the cycle, ligands are still present on day 14 in the cycle and in some patients on day 22 of the cycle, but no ligands were detected 60 days after CC treatment.

Amenorrhea↗

Toxic effects of cyclopiazonic acid in the early phase of pregnancy in mice.

The reproductive toxicity of a single oral dose/mouse (15-50 mg/kg) of cyclopiazonic acid (CPA) in the early phase of pregnancy (day 2-8) was investigated. Male mice used in this study were untreated. A limited number of pregnant mice were treated with 66 mg/kg ergonovine maleate (po, sc) to compare its effect with that of an equivalent dose of CPA (50 mg/kg). Among control sperm-positive mice treated with po NaHCO3 solution, 97.5% were gravid on necropsy day (pregnancy day 12). A single dose of CPA (15-50 mg/kg, po) given on days 2 to 8, decreased the pregnancy rates significantly. In groups treated with a single dose of CPA on pregnancy day 4 to 8, vaginal hemorrhage was observed 1 to 7 days after treatment, and it usually resulted in termination of pregnancy (abortion). Fetal resorption rates were higher than the control rate only in the groups treated with 30 mg/kg CPA po on day 4 or 8. CPA decreased body weight gains and the weights of uteri with fetuses. The ovary weights were generally not changed. Ergonovine maleate (66 mg/kg, sc, po) had no significant effect on all of the parameters examined. The estrous cycle returned without any delay in sperm-positive mice in which nidation of fertilized eggs had been inhibited by CPA, and also in nonpregnant mice (used for the LD50 determination) surviving near lethal doses of CPA (50-70 mg/kg, po). The oral LD50 value for CPA in nonpregnant mice was 64 +/- 4.4 mg/kg, and the toxicity signs were ptosis, hypokinesia, hypothermia, action tremor, cessation of food and water intake and resulting cachexia. The duration and intensity of these toxic signs were dose dependent.

Aging↗

The angioarchitecture of the Lewis lung carcinoma in laboratory mice (a light microscopic and scanning electron microscopic study).

53 Lewis lung carcinomas implanted subcutaneously into C57BL/6-mice were examined. The animals were killed at various stages of tumor growth (TG) and prepared for histology and for scanning electron microscopy (critical-point-dried tissue; vascular corrosion casts). Prior to casting animals were rinsed using different perfusion pressures. Casting was done by manual injection of the resin, whereby different influx-rates were applied resulting in low, medium and high pressure preparations. We discern 3 phases of tumor angiogenesis (TA) occurring during 4 stages of TG among which vasodilation establishes the first reaction of the host vascular system to a growing tumor implant. During this stage 1 of TG, tumor nidation, nearby sinusoidal dilated host capillaries form globular outgrowings (phase 1 of TA). Subsequently radially arranged sprouts, which preferentially arise from venous host vessels, grow into the centre of the implant (phase 2 of TA). Stage 2 of TG, early tumor growth, is characterized by necrosis of the central tumor tissue and the development of a central avascular cavity. Thus the tumor vascular system is organized like a hollow sphere with a central cavity and a peripheral vascular "envelope" with large vessels embracing the tumor and centrifugally growing vascular sprouts, which arise from the venous part of the vascular "envelope" and invade the surrounding host tissue (phase 3 of TA). During stage 3 of TG, late tumor growth, many vessels of the basket-like vascular "envelope" obliterate. In stage 4 of TG, prefinal phase, the peripheral vascular density decreases continuously. Thus vascular sprouting and proliferation of viable tumor cells is confined to basal regions of the tumor.

Arterioles↗

Abnormal placentation.

It is only relatively recently that attention has been directed to studies of the uterine side of the placenta to look for possible defects that might explain otherwise inexplicable pregnancy complications. Preeclampsia and intrauterine fetal growth retardation are two such disorders, in which new information has come to light by the study of placental bed biopsies and occasional cesarean hysterectomy specimens. It will be less easy to apply these techniques to such problems as spontaneous abortion and antepartum hemorrhage, but reemphasizing what should be the self-evident importance of the establishment and development of the uteroplacental blood supply might help reorient thinking about these and other important complications of pregnancy. Fresh thoughts are required too about the etiology and natural history of ectopic pregnancy, not so much for its own sake but more because of what it tells us about nidation and placentation in general. It is now difficult to insist on stringent criteria for the endometrium in human gestation, with all that this implies for the woman under investigation for infertility, when in some circumstances these criteria are flouted in what should be an alien mucosa. Much more needs to be known about the promotion and control exercised over trophoblastic differentiation and migration and interaction with uterine tissues. The uterus certainly can no longer be considered an immunologically privileged site even were that privilege extended to the fallopian tube and, indeed, to the adnexa generally. The constraining influence of decidua, if indeed it has such a property, requires elucidation; it cannot be fortuitous that only in species with hemochorial placentation, characterized by migratory nonvillous trophoblast, is a true stromal decidua formed. This surely indicates that decidua has a major role to play in negotiating "the treaty of compromise" ultimately signed between fetal and maternal tissues and if such a treaty is not signed, or is broken, defective placentation and its consequences must follow.

Abortion, Spontaneous↗

Etiology of cervical pregnancy. Association with abortion, pelvic pathology, IUDs and Asherman's syndrome.

Five cases of cervical pregnancy were treated with hysterectomy. In addition to previous pelvic pathology, iatrogenic interventions can be possible predisposing factors in this type of pregnancy. The association of cervical pregnancy and induced abortion, with traumatic curettage damaging the endometrium, rendering it unsuitable for nidation, is well documented. The two cases of severe intrauterine adhesions in our series suggest that partial or complete obliteration of the uterine cavity by such adhesions might be an important cause of cervical pregnancy. The presence of an IUD and the administration of hormonal therapy for the treatment of Asherman's syndrome might have contributed to our cases of cervical pregnancy.

Abortion, Induced↗

[The clinical picture and pathogenesis of cervical pregnancy].

A report is given on a true cervical pregnancy connected with placenta percreta destruens in the sixth month of pregnancy in a twenty six-years old woman after her first pregnancy had been interrupted. A pathogenetic correlation between the induced abortion and the cervical pregnancy seems to be very probably. A damaged cervix probably offers the fertilized egg a more convenient oppertunity for the nidation. The prognosis of those dramatic ectopic pregnancies firstly depends on the early decision on carrying out hysterectomy in order to stop the dangerous bleeding.

Abortion, Induced↗

[A successfully completed abdominal pregnancy].

The first pregnancy of a 22-year-old woman with somewhat more pronounced and prolonged symptoms of emersis gravidarum was followed up in the outpatient unit and was considered normal. The woman was admitted to the maternity ward 38 days before the term of labour because of painful abdominal cramps, vomiting and weakness. In the course of the first 17 days in hospital, the pregnancy was maintained by the use of spasmolytics but at that time it became clear on the basis of the symptoms, gynecological findings, and the gravidogram, that the case related to abdominal pregnancy. On the 18th day of hospitalization, laparotomy ws performed and a live, female, prematurely born baby, 2,450 g/45 cm, without any deformity, was delivered. The pregnancy was abdominal, with the nidation of the placenta at the right uterine horn. The placenta was completely removed. The girl is now 6 years old and her psychophysical development is normal, corresponding to her age.

Adult↗